Hydrochloric Acid → N-methyl-3-amino-5-tert-butyl-2-furancarboxamide

Temperature

0 °C

A slurry of methylamine hydrochloride (1.03 g, 15.2 mmol, 3.0 equiv) in anh. toluene (60 mL) at 0° C. was treated with AlMe3 (2M in toluene, 7.6 mL, 15.2 mmol, 3.0 equiv). The resulting solution was stirred at 0° C. for 30 min and allowed to warm to room temp for 40 min. To the aluminum amide solution was then added methyl 3-amino-5-tert-butyl-2-furancarboxylate (1.00 g, 5.1 mmol). The resulting mixture was heated at the reflux temp. for 20 h, cooled to room temp., and a 6N HCl solution was added dropwise. The quenched mixture was made basic with a 1N NaOH solution (approximately 100 mL) and extracted with EtOAc (3×200 mL). The combined organic layers were washed with a saturated NaCl solution, dried (Na2SO4), and concentrated under reduced pressure to afford N-methyl-3-amino-5-tert-butyl-2-furancarboxamide as a yellow solid (0.90 g, 91%): TLC (20% EtOAc/CH2Cl2) Rf0.26; 1H NMR (CDCl3) δ1.23 (s, 9H), 2.93 (d, J=4.8 Hz, 3H), 4.51 (br s, 1H), 5.73 (s, 1H).

1. temperatureto warm to room temp for 40 min
2. temperatureThe resulting mixture was heated at the reflux temp
3. waitfor 20 h
4. temperaturecooled to room temp.
5. extractionextracted with EtOAc (3×200 mL)
6. washThe combined organic layers were washed with a saturated NaCl solution
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated under reduced pressure

ORD record

ord-9e2af1b5401f4cb7ab2e670c0c7c7165

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06344476B1